The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti‐ageing ingredients

Gillbro, Johanna M.; Merinville, Eve; Olsson, Maja; Al-Bader, Tamara; Klack, A.; Visdal-Johnsen, Lene; Mavon, Alain

doi:10.1111/ics.12251

Cited by 14 publications

(10 citation statements)

References 69 publications

(84 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, Ty might be involved in Parkinson's disease development, through degradation of L ‐DOPA 11. In cosmetology, attention is focused on the development of tyrosinase inhibitors as skin‐whitening agents by silencing melanin formation 12. 13 In the food industry, tyrosinase inhibition (to reduce melanin synthesis) is being developed to control browning of fruit and vegetables 14–16…”

Section: Introductionmentioning

confidence: 99%

Investigation of Binding‐Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors

et al. 2014

View full text Add to dashboard Cite

Tyrosinase is a copper-containing enzyme found in plants and bacteria, as well as in humans, where it is involved in the biosynthesis of melanin-type pigments. Tyrosinase inhibitors have attracted remarkable research interest as whitening agents in cosmetology, antibrowning agents in food chemistry, and as therapeutics. In this context, commercially available tyrosinase from mushroom (TyM) is frequently used for the identification of inhibitors. This and bacterial tyrosinase (TyB) have been the subjects of intense biochemical and structural studies, including X-ray diffraction analysis, and this has led to the identification of structural homology and divergence among enzymes from different sources. To better understand the behavior of potential inhibitors of TyM and TyB, we selected the aurone family-previously identified as potential inhibitors of melanin biosynthesis in human melanocytes. In this study, a series of 24 aurones with different hydroxylation patterns at the A- and B-rings were evaluated on TyM and TyB. The results show that, depending on the hydroxylation pattern of A- and B-rings, aurones can behave as inhibitors, substrates, and activators of both enzymes. Computational analysis was performed to identify residues surrounding the aurones in the active sites of both enzymes and to rationalize the interactions. Our results highlight similarities and divergence in the behavior of TyM and TyB toward the same set of molecules.

show abstract

Section: Introductionmentioning

confidence: 99%

Investigation of Binding‐Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Overall, histological in vivo studies, to evaluate the efficacy of an anti‐ageing active, are still rare within the industry. Only a few such studies have been conducted to date in humans . Griffiths and his team tested a commercially available ‘anti‐ageing’ cream in 2009, which was shown to increase fibrillin‐1 deposition .…”

Section: Discussionmentioning

confidence: 99%

“…Gene array investigation of 30 000 genes with corresponding connectivity mapping after 7‐day topical application of RA, a gold standard for treatment of photoaged skin revealed A‐A‐A as a potential retinoid mimicking agent . The epidermal and dermal activity of A‐A‐A was also demonstrated in vitro showing (i) increased keratinocyte regeneration, (ii) relief of fibroblast stiffness and (iii) MMP inhibition .…”

Section: Discussionmentioning

confidence: 99%

“…Gene array investigation of 30 000 genes with corresponding connectivity mapping after 7‐day topical application of all‐trans retinoic acid (RA) on photodamaged skin revealed acetyl aspartic acid (A‐A‐A) as a potential and novel anti‐ageing ingredient , the activity of which was then demonstrated using an in silico and in vitro approach on epidermal and dermal cells .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo topical application of acetyl aspartic acid increases fibrillin‐1 and collagen IV deposition leading to a significant improvement of skin firmness

Gillbro

Merinville²,

Cattley³

et al. 2015

Intern J of Cosmetic Sci

Self Cite

View full text Add to dashboard Cite

Synopsis Objective Acetyl aspartic acid (A‐A‐A) was discovered through gene array analysis with corresponding Cmap analysis. We found that A‐A‐A increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F‐actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in‐use trial demonstrated that 1% A‐A‐A was well tolerated. In this study, the aim was to investigate whether A‐A‐A could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Method Two separate double‐blind vehicle‐controlled in vivo studies were conducted using a 1% A‐A‐A containing oil‐in‐water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12‐day treatment of A‐A‐A on collagen IV (COLIV) and fibrillin‐1. In a subsequent pilot study, 0.1% retinol was used for comparison to A‐A‐A (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Results Twelve‐day topical application of 1% A‐A‐A significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% A‐A‐A and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and A‐A‐A. However, only A‐A‐A exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of A‐A‐A as a skin‐firming active ingredient. Conclusion In this study, we showed the in vivo efficacy of 1% A‐A‐A both on a protein level (fibrillin and collagen IV) and on a clinical end point, specifically skin firmness, providing proof that, acetyl aspartic acid has a strong potential as an anti‐ageing ‘cosmeceutical’ ingredient answering the needs of our key consumer base.

show abstract

“…Previously, we identified acetyl aspartic acid (A‐A‐A) as a potential anti‐ageing ingredient by conducting a gene array on photodamaged, aged skin treated with all‐trans retinoic acid (RA) . The activity of retinoids on photoaged skin was identified decades ago.…”

Section: Introductionmentioning

confidence: 99%

Structural activity relationship analysis (SAR) and in vitro testing reveal the anti‐ageing potential activity of acetyl aspartic acid

Gillbro

Lundahl

Westman

et al. 2015

Intern J of Cosmetic Sci

Self Cite

View full text Add to dashboard Cite

Synopsis Background Acetyl aspartic acid (A‐A‐A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap), aiming for identification of new compounds with anti‐ageing properties. Objective The aim of this study was to use structural activity relationship (SAR) analysis to identify a predictive mechanism of action of A‐A‐A. The findings from SAR will be further characterized by in vitro activity testing. Furthermore, we aimed to investigate the role of polymerized filamentous F‐actin in ageing fibroblasts and to evaluate the effect of A‐A‐A on this model. Methods To predict the mode of action of A‐A‐A, we used the PASS computer program as a SAR model. In vitro, scratch motility tests with immortalized keratinocytes were used as a model for wound healing potential. Matrix metalloproteinase 1‐3 (MMP 1‐3) was analysed using multiplex protein assays (Luminex), and polymerized actin was detected by phalloidin staining in dermal fibroblasts (HDF). Results SAR analysis predicted that A‐A‐A would possess both epidermal and dermal activities with identification of wound healing and MMP inhibition potential. Further in vitro studies confirmed the wound healing potential using keratinocyte scratch motility assays. We were also able to confirm the dermal activities predicted by inhibition of MMP (MMP 1–3) in HDF by A‐A‐A. In addition, we found a positive relationship between age and F‐actin expression. We also discovered that stimulation of HDF with A‐A‐A for 72 h significantly reduced the polymerized cytoskeletal network as visualized by inhibition of F‐actin expression. In fact, A‐A‐A leveraged the expression of F‐actin in middle‐aged female fibroblasts (50 years of age) to the level of young female fibroblasts (30 years of age), corresponding to a 40% reduction in F‐actin expression. Conclusion Using an in silico and in vitro approach, we were able to demonstrate that A‐A‐A has the capacity to target different compartments of the skin through keratinocyte regeneration, MMP inhibition and relief in fibroblasts stiffness by reduction of F‐actin cytoskeletal network in HDF.

show abstract

The use of gene arrays and corresponding connectivity mapping (Cmap) to identify novel anti‐ageing ingredients

Cited by 14 publications

References 69 publications

Investigation of Binding‐Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors

Investigation of Binding‐Site Homology between Mushroom and Bacterial Tyrosinases by Using Aurones as Effectors

In vivo topical application of acetyl aspartic acid increases fibrillin‐1 and collagen IV deposition leading to a significant improvement of skin firmness

Structural activity relationship analysis (SAR) and in vitro testing reveal the anti‐ageing potential activity of acetyl aspartic acid

Contact Info

Product

Resources

About